Submissions for variant NM_024757.5(EHMT1):c.623C>T (p.Pro208Leu)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003108864	SCV003783330	uncertain significance	Kleefstra syndrome 1	2022-11-01	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals affected with EHMT1-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt EHMT1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 208 of the EHMT1 protein (p.Pro208Leu).
Laboratory of Genetics, Children's Clinical University Hospital Latvia	RCV003108864	SCV005045895	benign	Kleefstra syndrome 1		criteria provided, single submitter	curation